FORMATION AND ORIGIN OF BASAL LAMINA AND ANCHORING FIBRILS IN ADULT HUMAN SKIN

The purpose of this investigation was to study the formation and origin of basal lamina and anchoring fibrils in adult human skin. Epidermis and dermis were separated by "cold trypsinization." Viable epidermis and viable, inverted dermis were recombined and grafted to the chorioallantoic membrane of embryonated chicken eggs for varying periods up to 10 days. Basal lamina and anchoring fibrils were absent from the freshly trypsinized epidermis before grafting although hemidesmosomes and tonofilaments of the basal cells remained intact. Basal lamina and anchoring fibrils were absent from freshly cut, inverted surface of the dermis. Beginning 3 days after grafting, basal lamina was noted to form immediately subjacent to hemidesmosomes of epidermal basal cells at the epidermal-dermal interface. From the fifth to the seventh day after grafting, basal lamina became progressively more dense and extended to become continuous in many areas at the epidermal-dermal interface. Anchoring fibrils appeared first in grafts consisting of epidermis and viable dermis at five day cultivation and became progressively more numerous thereafter. In order to determine the epidermal versus dermal origin of basal lamina and anchoring fibrils, dermis was rendered nonviable by repeated freezing and thawing 10 times followed by recombination with viable epidermis. Formation of basal lamina occurred as readily in these recombinants of epidermis with freeze-thawed, nonviable dermis as with viable dermis, indicating that dermal viability was not essential for synthesis of basal lamina. This observation supports the concept of epidermal origin for basal lamina. Anchoring fibrils did not form in recombinants containing freeze-thawed dermis, indicating that dermal viability was required for anchoring fibrils formation. This observation supports the concept of dermal origin of anchoring fibrils.     

Ultrastructural studies of regenerating spines of the sea urchin Strongylocentrotus purpuratus I. Cell types without spherules

The fine structure of regenerating tips of spines of the sea urchin Strongylocentrotus purpuratus was investigated. Each conical tip consisted of an inner dermis, which deposits and contains the calcite skeleton, and an external layer of epidermis. Although cell types termed spherulecytes containing large, intracellular membrane bound spherules were also present in spine tissues, only epidermal and dermal cell types lacking such spherules are described in this paper. The epidermis was composed largely of free cells representing several functional types. Over the apical portion of the tip these cells occurred in groups, while proximally they were distributed within longitudinal grooves present along the periphery of the spine from the base to the tip. The terminal portions of apical processes extending from some of the epidermal cells formed a thin, contiguous outer layer consisting of small individual islands of cytoplasm bearing microvilli. Adjacent islands were connected around the periphery by a junctional complex extending roughly 200 Å in depth in which the opposing plasma membranes were separated by a narrow gap about 145 Å in width bridged by amorphous material. Other epidermal cells were closely associated with the basal lamina, which was 900 Å in thickness and delineated the dermoepidermal junction; some of these cells appeared to synthesize the lamina, while others may be sensory nerve cells. The dermis at the spine tip also consisted of several functional types of free cells; the most interesting of these was the calcoblast, which deposits the skeleton. Calcoblasts extended a thin, cytoplasmic skeletal sheath which surrounded the tips and adjacent proximal portions of each of the longitudinally oriented microspines comprising the regenerating skeleton, and distally, formed a conical extracellular channel ahead of the mineralizing tip. The intimate relationship between calcoblasts and the growing mineral surface strongly suggests that these cells directly control both the kinetics of mineral deposition and morphogenesis of the skeleton. Other cell types in the dermis were precalcoblasts and phagocytes. Precalcoblasts may function as fibroblasts and are possible precursors of calcoblasts. Closely associated with the basal lamina at the dermoepidermal junction were extracellular unbanded anchoring fibrils 150 Å to 200 Å in diameter. Scattered proximally among dermal cells were other extracellular fibrils, presumably collagenous, about 300 Å in diameter with a banding periodicity of 210 Å.     

Nervous system of ascidian larvae: Caudal primary sensory neurons

Summary In larvae of Diplosoma macdonaldi one sensory nerve extends along the dorsal midline of the tail and another extends along the ventral midline. Each nerve is composed of 50–70 naked axons lying in a groove in the base of the epidermis, and each projects to the visceral ganglion. The cell bodies of the caudal sensory neurons occur in pairs within the epidermis, and are situated along the courses of the nerves. A single cilium arises from an invagination in the soma of each neuron, passes through the inner cuticular layer of the tunic and enters a tail fin formed by the outer cuticular layer. We propose that these cells are mechanoreceptors. The caudal sensory system is similar in representative species of ten families of ascidians.Abbreviations a axial complex of the tail - ac accessory centriole - ax axon - bb basal body - bl basal lamina - c cilium - cep common epidermal cells - cs ciliary sheath - dcv dense-cored vesicles - dsn dorsal sensory nerve - ec ependymal cells - ep epidermis - gj gap junction - h hemocoel - hc hemocoelic chamber - icl inner cuticular layer of the tunic - m caudal muscle - nc dorsal nerve cord - ncl neurocoel - no notochord - ocl outer cuticular layer of the tunic - sc sensory cell - sn sensory nerve - sv sensory vesicle - vg visceral ganglion - vsn ventral sensory nerve     

The ultrastructure and formation of the calcareous ossicles in the body wall of the sea cucumber Leptosynapta clarki (Echinodermata,Holothuroida)

Summary The calcareous ossicles of the burrowing sea cucumber Leptosynapta clarki have been examined by scanning and transmission electron microscopy. The ossicles occur in the dermis of the body wall and comprise three main types: 1) curved rods; 2) miliary granules; and 3) anchorshaped structures that are paired with oval plates. Rods average about 80 m in length, and miliary granules are typically 20–30 m long. Both of these ossicles appear to form a protective skeleton in regions where the water vascular system and accompanying nerves are located. Anchors and plates are scattered throughout the interambulacra of the body at densities ranging from 2–8/mm². Each anchor measures about 145 m long and is attached to the plate underlying it by a flexible ligament that is composed of collagen fibrils. Tetracycline labeling studies indicate that anchors and plates take several months to reach full size. All developing ossicles appear to be surrounded by a syncytial network of sclerocytes that characteristically possess numerous mitochondria and a conspicuous external lamina. Fully formed anchors lie directly beneath the epidermis and do not protrude through the outermost layer of the body wall. During burrowing, the curved flukes of the anchorshaped ossicles may provide added traction as the buccal tentacles dig through the sediment.List of abbreviations a anchor - ar ambulacral region - cm circular muscle layer of body wall - cs cytoplasmic sheath - d dermis - ep epidermis - f fluke - ild inner layer of dermis - k keel - me myoepithelium - mg miliary granule - n nerve - old outer layer of dermis - os ossicle - pl plate - s sclerocyte - sh shank - st stock     

Fine structure of the epidermis in Gnathostomulida

Summary The fine structure of the epidermis in Haplognathia simplex, Haplognathia rosea, Pterognathia meixneri (Filospermoidea) and Gnathostomula paradoxa (Bursovaginoidea) has been investigated. The epidermis in the filospermoidean species is uniform, consisting of epidermal cells with a single locomotory cilium. The structure and development, including ciliogenesis, of these epidermal cells are described. In G. paradoxa additional epidermal elements have been found: mucous cells with a presumably apocrine secretion modus are scattered in a strip-like arrangement within the epidermis. Their deverlopment is separate from epidermal cells with locomotory function. Two further types of glandular cells with either a single cilium or a diplosome are located ventrally. It is assumed that they represent an adhesive system.Abbreviations (used in figures) ac accessory centriole - ap appendix of accessory centriole - ax axoneme - bb basal body - bf basal foot - bl basal lamina - c cilium - cA ciliary adhesive cell - ce centriole - cp ciliary pit - d diplosome - dy dictyosome - dA diplosomal adhesive cell - E epidermal cell with locomotory cilium, epidermis - ev epidermal vesicle (epitheliosome) - gv gland vesicle - m mitochondrion - ma microvillus of apical cell membrane - mp microvillus of ciliary pit - mv microvillus - n nucleus - ps prosecretory-vesicle - R receptor - r ciliary rootlet - rc caudal ciliary rootlet - rr rostral ciliary rootlert - sv secretory vesicle - v vesicle - v _i central vesicle of multivesicular body - v _o surrounding vesicle of multivesicular body - z cisternae     

A new type of somatosensory organ in the nasolabial skin of the dog

A new morphological type of somatosensory organ is described. It is found in the glabrous skin of the dog nose (rhinarium or planum nasale) and situated in dermis papillae. The otherwise thick epidermis forms a thin window above the organ. There are only a few layers of keratinocytes in the window and the corneocytes are much thinner than elsewhere. The organ consists of highly branching cells that wrap naked nerve endings emanating from myelinated nerve fibers originating in the outer dermal nerve plexus. The structure entirely fills the top of the dermal papilla. The intercellular spaces of the organ and its surroundings are occupied by an extended areolar basal lamina.     

Development of sensory innervation in chick skin: comparison of nerve fibre and chondroitin sulphate distributions in vivo and in vitro

In bird skin, nerve fibres develop in the dermis but do not enter the epidermis. In co-cultures of 7-day-old chick embryo dorsal root ganglia and epidermis, the neurites also avoid the epidermis. Previous studies have shown that chondroitin sulphate proteoglycans may be involved. Chondroitin sulphate has therefore been visualized by immunocytochemistry, using themonoclonal antibody CS-56, both in vivo and in vitro using light and electron microscopy. Its distribution was compared to those of 2 other chondroitin sulphate epitopes and to that of the growing nerve fibres. In cultures of epidermis from 7-day-old embryonic chicks, immunoreactivity is found uniformly around the epidermal cells while at 7.5 days the distribution in dermis is heterogeneous, and particularly marked in feather buds. In vivo, chondroitin sulphate immunoreactivity is detected in the epidermis, on the basal lamina, on the surfaces of fibroblasts and along collagen fibrils. This localization is complementary to the distribution of cutaneous nerves. Chondroitin sulphate in the basal lamina could prevent innervation of the epidermis and the dermal heterogeneities could partly explain the nerve fibres surrounding the base of the feathers. Chondroitin sulphate could therefore be important for neural guidance in developing chick skin.     

Functional organization of the skin of the ‘Green-puffer fish’Tetraodon fluviatilis (Ham.-Buch.) (Tetraodontidae,Pisces)

Summary The present study concerns the functional organization of the skin ofTetraodon fluviatilis. The epidermis consists of five different types of cells — the flask-shaped mucous cells, the eosinophilic granular cells, the sacciform granulated cells, the vesicle containing granulated cells, and the polygonal cells. A thin noncellular layer, the cuticle found on the surface of the skin, is probably secreted from the polygonal cells in the outermost layer of the epidermis. A,well-defined lymphatic plexus exists between the cells of the basal layer.Numerous triradiate calcareous spines are embedded within elastic connective tissue pockets in the thick dermis. These pockets are filled with an amorphous, acellular, PAS positive material, and are richly supplied with fine blood capillaries. A histomorphologic basis for the erection of the spines and various structural modifications in the skin facilitating its enormous stretching under inflated conditions of the fish are discussed.Abbreviations Used BCA blood capillary - BM basement membrane - BC basal cell - BL basal layer - CFB collagen fiber bundle - CTB connective tissue band - DER dermis - EGC eosinophilic granular cell - EPD epidermis - FB fibroblasts - FC fat cell - L lymphocyte - LS lymphatic space - MC mucous cell - ML middle layer - MUS muscle - MYS myocommata - NV nerve - OL outermost layer - PCB black pigment cell - PCY yellow pigment cell - PEC polygonal epidermal cell - SCT subcutis - SGC sacciform granulated cell - SP spine - STC stratum compactum - STL stratum laxum - VGC vesicle containing granulated cell - VS vertical strand This investigation was supported by a research grant No. 38(131)/72-GAU-II from the Council of Scientific and Industrial Research and a financial assistance grant for teachers No. F. 6(4626) 72-(SF-1), from the University Grants Commission, Government of India, New Delhi.     

Ultrastructure of gill epithelial cells of Diopatra neapolitana (Annelida,Polychaeta)

Summary The ultrastructure of gill epidermal cells of Diopatra neapolitana and their relationship with blood spaces are described. The existence of a basal infolding complex, related to the blood spaces, is also reported. A possible involvement of these cells in osmoregulation and ion interchange, apart from their well-known role in respiration, is suggested.Abbreviations bc Blood cell - bi Basal infolding - bl Basal lamina - bs Blood space - ci Cilia - cu Cuticle - db Dense body - EC Epidermal cell - Gc Golgi complex - id Interdigitation - j Junction - m Mitochondria - mv Microvilli - n Nucleus - pv Pinocytotic vesicle - rer Rough endoplasmic reticulum     

Subsurface sense receptors in the larva of Austramphilina elongata Johnston, 1931 (Amphilinidea)

Summary The ultrastructure of tegumental and subtegumental receptors in the larva of Austramphilina elongata is described. The receptors are terminal swellings of dendrites and contain numerous small vesicles and neurofilaments which are predominantly peripheral. Tegumental receptors, together with a sheath consisting of basal lamina and tegument, project into the epidermis, and cross-striated rootlets were sometimes found in them. Subtegumental receptors lie below the tegument and ciliary rootlets were never observed in them. Anterior dendrites contain single centrioles and clusters of centrioles. The possible function of receptors and centrioles is discussed.Abbreviations in figures bl basal lamina - c centriole - d dendrite - ep epidermis - m microvillus - nt neurotubules - r rootlet of cilium - re receptor - st subtegumental receptor - t tegument     

Topographical and developmental studies on target sites of 1,25 (OH2) vitamin D3 in skin

Summary Tritium-labeled 1,25 (OH₂) vitamin D₃, when injected into vitamin D-deficient adult and pregnant rats is concentrated and retained strongest in nuclei of cells in the outer root sheath of the hair, followed by the stratum granulosum, spinosum, and basale of the epidermis. In the hair follicle, in addition to the most heavily labeled outer root sheath, nuclear labeling exists also in cells of the hair bulb and of the inner root sheath, as well as in basal cells of the sebaceous gland. In contrast, cells of the dermal papilla and the connective tissue of the dermis are generally unlabeled, except for labeled cells in the outer connective tissue sheath at the infundibulum of vibrissae of 20-day fetal rats and a few scattered labeled cells in the dermis, probably macrophages. In the developing hair, in 18- and 20-day fetal rats, a distinct topographic pattern of labeled cells can be seen, which is characteristic of the different stages of hair follicle development. In the hair germ, heavily labeled cells appear first in the stratum spinosum. In the hair peg, they remain in this position in its juxtaepidermal portion; however, when a dermal papilla develops, heavily labeled cells assume a marginal position. This suggests a sequential epidermal-epidermal and mesenchymal-epidermal receptor induction. Injection of tritium labeled 25 (OH) vitamin D₃ did not show nuclear concentration in these tissues and excess unlabeled 25 (OH) vitamin D₃ — unlike excess 1,25 (OH₂) vitamin D₃ — did not prevent nuclear uptake of tritium labeled 1,25 (OH₂) vitamin D₃. The results indicate differential effects of 1,25 (OH₂) vitamin D₃ on different structures in the epidermis and dermis.Supported by US PHS grant PCM8200569     

Light and electron microscopic studies of the skin of the Palembang puffer,Tetraodon steindachneri (Teleostei,Tetraodontidae)

Summary The skin ofTetraodon steindachneri is morphologically and cytologically adapted to the habits and locomotion of the fish, as well as to its ability to expand its body into a nearly spherical shape. Negative buoyancy, which facilitates precise maneuvers near the bottom, is achieved primarily by a very thick dermis. Various special features of the skin enable it to withstand the mechanical stresses of extreme expansion and deep folding: (1) the absence of a covering such as a cuticle on the outer surface of the epidermis, (2) the lack of scales, (3) the pronounced interdigitation of the epidermal cells, (4) the cytoskeleton of the filament-containing cells, and (5) the stratum compactum of the dermis. The spines, which inT. steindachneri can be extended and retracted, are derived, like the spines of diodontidae, from the scales of other teleosts. Each spine comprises cellular and acellular components, which together produce a complicated bilaterally symmetrical structure. Movement of the spines is mainly a passive mechanical concomitant of distension of the body, though active processes cannot be ruled out. The biological significance of the spine apparatus ofT. steindachneri is discussed.Abbreviations af annular fold - amc apical mucous cell - bv blood vessel - bm basal membrane - cf collagen fibers - cfb collagen fiber band - cv central vacuole - d desmosome - de dermis - ed epidermis - f tonofilaments - fcc filament-containing cell - gc granular cell - id interdigitation - md modified dermis - mr microridges - n nucleus - nf nerve fibers - s spine - sc stratum compactum - sk skeleton of spine - sl stratum laxum - smc sacciform mucous cell - sub subcutis - vc vacuole cell     

Observations on the ultrastructure and distribution of chromatophores in the skin of chelonians

Alibardi, L. 2011. Observations on the ultrastructure and distribution of chromatophores in the skin of chelonians. —Acta Zoologica (Stockholm) 00 :1–11. The cytology and distribution of chromatophores responsible for skin pigmentation in chelonians is analyzed. Epidermal melanocytes are involved in the formation of dark spots or stripes in growing shelled and non‐shelled skin. Melanocytes rest in the basal layer of the epidermis and transfer melanosomes into keratinocytes during epidermal growth. Dermal melanophores and other chromatophores instead remain in the dermis and form the gray background of the skin. When dermal melanophores condense, they give origin to the dense spots or stripes in areas where no epidermal melanocytes are present. In the latter case, the epidermis and the corneous layer are transparent and reveal the dermal distribution of melanophores and other chromatophores underneath. As a result of this basic process of distribution of pigment cells, the dark areas visible in scales can have a double origin (epidermal and dermal) or a single origin (epidermal or dermal). Xanthophores, lipophores, and a cell containing both pterinosomes and lipid droplets are sparse in the loose dermis while iridophores are rarely seen in the skin of chelonians analyzed in the present study. Xanthophores and lipophores contribute to form the pale, yellow or oranges hues present among the dark areas of the skin in turtles.     

Fat distribution in the skin of bottlenose dolphins (Tursiops truncatus and Tursiops gilli)

Frozen sections stained with Oil-red-O and semithin (0.5 μm) plastic sections stained with toluidine blue revealed an abundance of fat globules of various sizes in all strata of the epidermis of bottlenose dolphins (Tursiops truncatus and T. gilli). The fat was rather evenly distributed but sometimes appeared as circumscribed areas of heavier concentration involving hundreds of cells (as seen in a single plane). Occasionally, there were smaller groups of epidermal cells heavily loaded with lipid. The dermis presented a unique phenomenon in the presence of abundant extracellular fat distributed among the collagen bundles as droplets of various sizes or as larger, irregularly shaped lipid particles that seemed to conform to the spaces between collagen bundles. These lipid particles were sometimes seen to be closely applied to the dermal surface of the stratum basale. Equally unusual was the presence of lipid particles of various sizes and shapes in the lumen of some of the vessels of the dermal papillae. Granular cells resembling mast cells were commonly seen in the papillary dermis and some were closely associated with lipid particles. Blood vessels of the reticular dermis tended to have collections of lipid droplets in the loose connective tissue often found adjacent to the tunica adventitia. It is postulated that the extracellular dermal lipids (probably mainly triglycerides) are broken down to free fatty acids that diffuse into the basal layer of the epidermis and are there resynthesized into triglycerides. Possible uses for the epidermal lipids are discussed.     

Cicatrization of the skin of the 7-day-old chick embryo cultured in vitro

A morphological study of in vitro wound healing has been performed by light, transmission and scanning electron microscopy in dorsal thoraco-lumbar skin of 7-day chick embryos. A circular wound, 750 microns in diameter, was punched out of dorsal skin, removing epidermis and the underlying dense dermis. Wound closure was completed within 96 to 120 hours. Feather bud development was not observed at the wound site. The epidermis began to migrate some 24 h after the wounding; the migration of peridermal cells preceded that of basal epidermal cells by some 12 hours. Mechanisms of the epidermal migration were similar to those observed in situ during wound healing of the integument in 5-day chick embryos (THEVENET, 1981), Superficial epithelization of bare dermis occurred as soon as 12 h after the injury. Cytoplasm of dermal cells exhibited many microtubules and a dilated rough endoplasmic reticulum. During the first 48 h, the epidermal cells established direct contacts and zones of close parallel apposition with epithelized dermal cell processes. The basement membrane lamina densa was maintained at the edges of the wound without retraction or ruffling. It was reconstituted concomitantly with the epidermal migration within 72 h. Cytoplasm of migratory epidermal and epithelized dermal cells exhibited many cytoskeleton structures.     

Cellular and extracellular involvement in the regeneration of the rat lower vibrissa follicle.

The sequence of events leading to the reconstruction of a fibre-producing hair follicle, after microsurgical amputation of the lower follicle bulb, has been detailed by immunohistology and electron microscopy. The initial response was essentially found to be a wound reaction, in that hyperproliferative follicle epidermis quickly spread to below the level of amputation--associated with downward movement of mesenchymal (or dermal) sheath cells. Fibronectin was prominent in both dermis and epidermis at this stage and, as in wound repair, preceded laminin and type IV collagen in covering the lower dermal-epidermal junction. Once a new basal line of epidermis and a complete basement membrane were established, laminin and type IV collagen were detected below this junction and within the prospective papilla-forming mesenchyme. This coincided with ultrastructural observations of profuse sub-basement membrane extracellular material in the region of new papilla formation. The glassy membrane displayed extensive ultrastructural modifications at its lower level, and these corresponded with localized variations in staining intensities for all three antibodies over time. The membrane hung below the level of the epidermis, and was crossed by migrating cells from the mesenchymal dermal sheath of the follicle - it acted to segregate the inner group of follicular dermal cells from wound fibroblasts. Extracellular matrix may be a mediator of the dermal-epidermal interactions associated with this hair follicle regeneration phenomenon.     

Ultrastructure of copulatory organs in Turbellaria

Summary The copulatory organs in Macrostomum sp. and Microstomum sp. contain simple tubular stylets which are intracellular specializations. The stylet in Macrostomum sp. is produced in a syncytium covering part of the prostatic vesicle. The proximal region of the stylet surrounds the vesicle which contains six prostatic gland ducts and six accessory (sensory) cells containing ciliary rootlets. The stylet in Microstomum sp. is produced in an extension of a syncytium which lines the combined seminal-prostatic vesicle. The stylet is connected to the combined vesicle by a narrow bridge of matrix syncytium through which sperm, prostatic gland products and sensory cilia pass from the vesicle to the stylet lumen. In both species the matrix syncytium can be interpreted as a specialized terminal end of the male canal epithelium. Stylets of Turbellaria and other lower Metazoa are discussed in regards to structure (one or several pieces) and location (in separate cells, in a syncytium, or extracellular).Abbreviations used in figures ac accessory cell - b basal body - c cilium - cv combined vesicle - d prostatic gland duct - dc degenerative cell - di dictyosome - e epidermis - ed ejaculatory duct - g prostatic gland cell - h hemidesmosome - i intercellular matrix - im internal muscle - in intestine; - l lumen of male canal - lm longitudinal muscle - m matrix syncytium - mc male canal epithelial cell - mi microfilaments - mt microtubules - mu muscle cell - mv microvilli - n nucleus - np nerve process - ns neurosecretory (?) granule - p prostatic vesicle - pv prostatic part of combined vesicle - r rootlet - s stylet - sm stylet material - sp sperm - sv seminal part of combined vesicle     

The Three-Dimensional Human Skin Reconstruct Model: a Tool to Study Normal Skin and Melanoma Progression

Most in vitro studies in experimental skin biology have been done in 2-dimensional (2D) monocultures, while accumulating evidence suggests that cells behave differently when they are grown within a 3D extra-cellular matrix and also interact with other cells (1-5). Mouse models have been broadly utilized to study tissue morphogenesis in vivo. However mouse and human skin have significant differences in cellular architecture and physiology, which makes it difficult to extrapolate mouse studies to humans. Since melanocytes in mouse skin are mostly localized in hair follicles, they have distinct biological properties from those of humans, which locate primarily at the basal layer of the epidermis. The recent development of 3D human skin reconstruct models has enabled the field to investigate cell-matrix and cell-cell interactions between different cell types. The reconstructs consist of a "dermis" with fibroblasts embedded in a collagen I matrix, an "epidermis", which is comprised of stratified, differentiated keratinocytes and a functional basement membrane, which separates epidermis from dermis. Collagen provides scaffolding, nutrient delivery, and potential for cell-to-cell interaction. The 3D skin models incorporating melanocytic cells recapitulate natural features of melanocyte homeostasis and melanoma progression in human skin. As in vivo, melanocytes in reconstructed skin are localized at the basement membrane interspersed with basal layer keratinocytes. Melanoma cells exhibit the same characteristics reflecting the original tumor stage (RGP, VGP and metastatic melanoma cells) in vivo. Recently, dermal stem cells have been identified in the human dermis (6). These multi-potent stem cells can migrate to the epidermis and differentiate to melanocytes.